Leishmaniasis, one of the leading tropical diseases in the world, is caused by infection with different species of the protozoan parasite Leishmania which is transmitted by sandfly. Clinically, leishmaniases can be classified into three groups, i.e.,cutaneous, mucocutaneous and the fatal visceral leishmaniasis. Therefore, Leishmania sap. are morphologically similar, but epidemiologically diverse and complex. The development of safe and effective vaccine is deemed as essential to control leishmaniasis. There are two forms in the life cycle of the Leishmania: (1) the promastigote, an extracellular flagellated form in the sandfly gut, and (2) the mastigote, an obligate intracellular non-motile form that resides in the macrophage of the vertebrate host. The molecular mechanism of stage differentiation and how Leishmania survive in the macrophage are of immense interest. This study aims to identify the surface receptor(s) and signal transduction pathway(s) responsible for the stage differentiation, as well as to identify the clinically important and tropism-related genes using molecular biological and genetic approaches. This work will be the basis for vaccine development.